POLYMORPHIC MEMBRANE PROTEINS OF CHLAMYDIA TRACHOMATIS

沙眼衣原体的多态性膜蛋白

• 批准号: 8068155
• 负责人: PATRIK M BAVOIL
• 金额: $ 7.23万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-10 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8068155
• 关键词: Antibodies; Antibody Formation; Antigen Targeting; Antigens; Archives; Biology; Body Surface; Brassicaceae; Cavia; Cells; Chlamydia; Chlamydia trachomatis; Chlamydophila pneumoniae; Chlamydophila psittaci; Clinical; Complex; Confocal Microscopy; Development; Disease; Disease Outcome; Dot Immunoblotting; Family; Fluorescence Microscopy; Frameshift Mutation; Gene Duplication; Gene Expression; Genes; Genetic Polymorphism; Genital system; Genomics; Human; Hybridomas; Immune; Immunization; Immunoblotting; Immunoelectron Microscopy; Immunofluorescence Immunologic; In Vitro; Individual; Infection; Kinetics; Lasers; Longitudinal Studies; Membrane; Membrane Proteins; Molecular; Molecular Profiling; Monoclonal Antibodies; Mus; Pathogenesis; Patients; Pattern; Pelvic Inflammatory Disease; Proteins; Recombinants; Role; Scanning; Screening procedure; Serum; Staging; Surface; Vaccine Design; member; patient population; polyclonal antibody; protein expression; research study; response

DESCRIPTION (provided by applicant): Chlamydial polymorphic membrane proteins (Pmps) are a newly identified family of Chlamydia-specific membrane proteins, whose role in chlamydial biology and pathogenesis is unknown. Genomic analysis of the pmp family of C. pneumoniae have revealed frameshift mutations, deletions and gene duplications. Studies of the larger pmp families of C. pneumoniae and C. psittaci have also revealed that Pmp proteins are expressed in vitro, that some can be detected at the elementary body surface, and that some are dominant antigens during infection and may be targets for vaccine design. The emerging evidence is consistent with a role of the pmp family in pathogenesis and immune evasion. The purpose of this project is to characterize the smallest pmp family identified to date: the 9-member pmp family of C. trachomatis. In preliminary studies using the 9 partially purified recombinant Pmps as target antigens, we have observed differential Pmp-specific antibody responses in archived sera from patients with pelvic inflammatory disease. This analysis will be expanded through cross-sectional and longitudinal comparisons of Pmp-specific responses in a well-characterized patient population with genital C. trachomatis l infection. This analysis may identify direct relationships between Pmp-specific responses and disease outcome. More importantly, this analysis will provide a set of fresh clinical C. trachomatis isolates for further I molecular characterization. A second focus of this project will be to identify and characterize determinants of pmp expression in C. trachomatis. Polymorphisms will be identified and compared in the pmp families of selected study isolates. Experiments will be performed to characterize developmental patterns of pmp expression in these isolates. Using a panel of Pmp-specific monoclonal and polyclonal antibodies generated in this project, we will examine Pmp protein expression and eventual translocation to the surface of the outer membrane along development and at the single cell level using laser scanning confocal fluorescence microscopy.

描述（由申请方提供）：衣原体多态性膜蛋白（Pmps）是一个新发现的衣原体特异性膜蛋白家族，其在衣原体生物学和发病机制中的作用尚不清楚。C. pmp家族的基因组分析肺炎链球菌已经揭示了移码突变、缺失和基因重复。对C.肺炎衣原体和C.鹦鹉热还揭示了Pmp蛋白在体外表达，一些可以在基本体表检测到，并且一些是感染期间的优势抗原，并且可以是疫苗设计的靶点。新出现的证据与pmp家族在发病机制和免疫逃避中的作用一致。 本项目的目的是表征迄今为止发现的最小的pmp家族：C.沙眼在初步研究中，使用9个部分纯化的重组PMPs作为靶抗原，我们已经观察到不同的PMPs特异性抗体反应，从盆腔炎患者的存档血清。通过在一个特征明确的生殖器丙型肝炎患者人群中对Pmp特异性反应进行横向和纵向比较，将扩展该分析。沙眼感染这种分析可以确定Pmp特异性反应和疾病结果之间的直接关系。更重要的是，这一分析将提供一组新鲜的临床C。沙眼分离物用于进一步的分子表征。本项目的第二个重点是鉴定和表征C.沙眼将在选定的研究分离株的pmp家族中鉴定和比较多态性。将进行实验以表征这些分离株中pmp表达的发育模式。使用本项目中产生的Pmp特异性单克隆抗体和多克隆抗体，我们将研究Pmp蛋白表达和最终易位到外膜表面沿着发展，并在单细胞水平上使用激光扫描共聚焦荧光显微镜。